title: Local calprotectin production in colorectal cancer and polyps--active neutrophil recruitment in carcinogenesis.
abstract: OBJECTIVE
  The aim of this study is to examine the expression level and localization of calprotectin in cancer tissue, tumor-adjacent mucosa, and polyps in colonic biopsies. Calprotection expression was correlated with neutrophil infiltration, markers of bacteremia, and systemic inflammation.
  
  
  METHODS
  Patients with colorectal cancer (n = 28) and adenoma (n = 38) were compared with healthy controls (n = 33). Calprotectin expression levels were measured by ELISA, and its localization was visualized by immunohistochemistry and correlated with the degree of neutrophil infiltration (visualized by Esterase staining). The expression of tumor necrosis factor (TNF)-alpha, procalcitonin, endotoxemia, carcinoembryonic antigen (CEA), and C-reactive protein was also investigated.
  
  
  RESULTS
  Mucosal calprotectin was expressed in significantly higher concentrations in carcinoma (94.2 ± 31.2 ng/mg total protein) and adenoma (122.8 ± 60.3 ng/mg total protein) in comparison with mucosal biopsies from healthy controls (20.4 ± 5.4 ng/mg total protein), tumor-adjacent mucosa from patients with colorectal carcinoma (21.6 ± 5.1 ng/mg total protein), and adenoma (45 ± 14.6 ng/mg total protein, all p < 0.05). Immunohistochemistry showed calprotectin reactivity mainly in granulocytes and macrophages with only singular reactive epithelial cells. Positive staining (quantified by the number of positive cells per square millimeter) was markedly increased in carcinoma tissue (85 ± 21.5) and in adenoma (67.5 ± 20) as compared with tumor-adjacent epithelia (18.8 ± 4.3, p = 0.0007, p = 0.003, respectively), and there was a highly significant correlation, r = 0.89, p = 0.001) between calprotectin staining and neutrophil infiltration. No significant differences were found in the systemic levels of TNF-alpha, procalcitonin, and endotoxemia, whereas CEA and C-reactive protein levels were significantly higher in the cancer group (p < 0.05).
  
  
  CONCLUSIONS
  Our results support the evidence that increased calprotectin expression is an early step in the neoplastic transformation during colorectal carcinogenesis. Moreover, its expression is closely related to an inflammatory response and points out a possible biological link between inflammation and neoplastic transformation in colorectal cancer.
authors.affiliation: First Department of Medicine, University Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany.
authors.forename: Kim
authors.initials: K
authors.lastname: Luley
authors.forename: Frank
authors.initials: F
authors.lastname: Noack
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Nils
authors.initials: N
authors.lastname: Homann
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D003111:Colonic Polyps / Q000276:immunology* / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000097:blood / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D020556:Neutrophil Infiltration / Q000276:immunology*; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D039841:Leukocyte L1 Antigen Complex